Longitudinal map of transcriptome changes in the Lyme pathogen Borrelia burgdorferi during tick-borne transmission

Borrelia burgdorferi (Bb), the causative agent of Lyme disease, must adapt to vastly different environments as the bacterium cycles between the tick vector and a vertebrate host. During a bloodmeal, Bb migrates from the tick midgut to the salivary glands and changes its gene expression, priming Bb for vertebrate infection. These tick-specific transmission events are dependent on key transcriptional regulators; however, the full range of transcriptional changes that occur over several days inside of the tick are technically challenging to capture. We developed an experimental approach to enrich Bb cells from Ixodes ticks during a transmitting bloodmeal to longitudinally define their global transcriptomic landscape. We identified 192 genes that substantially change expression over the course of the tick bloodmeal, most of which were located on plasmids of the Bb genome. The majority of upregulated genes encode proteins found at the cell envelope or proteins of unknown function, including 45 outer surface lipoproteins embedded in the unusual protein-rich coat of Bb. As these proteins may facilitate Bb interactions with host tissues or immune systems, we also utilized mass spectrometry to identify candidate tick proteins that physically associate with Bb. The ex vivo Bb transcriptomes and candidate tick interacting proteins presented here provide an important roadmap for investigating key determinants of Bb priming and transmission during the tick stage of its unique transmission cycle. ### Competing Interest Statement Seemay Chou is president and CEO of Arcadia Biosciences.